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  • ÀüÀӺα³¼ö(ÀÇ°ú´ëÇÐ)
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  • 2000-2012 Æ÷Ç×°ø°ú´ëÇб³ »ý¸í°úÇаú, Çлç / ¹Ú»ç
    2012-2019 ¿¡¸ð¸®´ëÇб³ ¹Ì»ý¹° ¹× ¸é¿ªÇаú, ¹Ú»çÈÄ / Ã¥ÀÓ / ¼ö¼® ¿¬±¸¿ø
    2020-present ¼º±Õ°ü´ëÇб³ ÀÇ°ú´ëÇÐ, Á¶±³¼ö

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  • º» ¿¬±¸½ÇÀº ¸¸¼º ¹ÙÀÌ·¯½º °¨¿°, ¾Ï, ÀÚ°¡¸é¿ªÁúȯ µîÀÇ ¸ðµ¨¿¡¼­ T¼¼Æ÷ ¸é¿ª¹ÝÀÀ¿¡ ´ëÇÑ º¸´Ù ±íÀº ÀÌÇظ¦ ¸ñÇ¥·Î ÇÔ. ±×¸®°í ÀÌ·¯ÇÑ ÀÌÇظ¦ ¹ÙÅÁÀ¸·Î Áúȯ ¸ðµ¨µé¿¡ ´ëÇÑ »õ·Î¿î ¸é¿ªÄ¡·á¹ýÀ» °³¹ßÇÏ´Â °ÍÀ» ÃÖÁ¾ ¸ñÇ¥·Î ÇÏ°í ÀÖÀ½.

    A. T¼¼Æ÷ ±â´ÉÀúÇÏ ±âÀÛ¿¡ °üÇÑ ¿¬±¸
    ±Þ¼º °¨¿°À̳ª ¹é½ÅÀÇ °æ¿ì, ±â¾ï T¼¼Æ÷¸¦ ¸¸µé°í, À̸¦ ÅëÇÏ¿© µ¿ÀÏÇÑ º´¿ø±Õ¿¡ ´Ù½Ã ³ëÃâµÇ¾úÀ» ¶§, È¿°úÀûÀ¸·Î ºü¸£°Ô Á¦°ÅÇÒ ¼ö ÀÖ°Ô µÊ. ÇÏÁö¸¸ ¸¸¼º °¨¿°À̳ª ¾Ï ¸ðµ¨ÀÇ °æ¿ì, ±â¾ï T¼¼Æ÷¸¦ ¸¸µéÁö ¸øÇÏ°í, °è¼ÓÀûÀÎ Ç׿ø Àڱذú ÇÔ²² T¼¼Æ÷ÀÇ ±â´ÉÀÌ Á¡Â÷ÀûÀ¸·Î °¨¼ÒÇÏ°Ô µÇ´Âµ¥, À̸¦ T¼¼Æ÷ ±â´ÉÀúÇÏ (T cell exhaustion)¶ó°í ÇÔ.
    º» ¿¬±¸ÆÀÀº ¸¶¿ì½º¸¦ ÀÌ¿ëÇÑ ¸¸¼º ¸²ÇÁ±¸¼º ¸Æ¶ô¼ö¸·¿°¹ÙÀÌ·¯½º (LCMV, lymphocytic choriomeningitis virus) °¨¿° ¸ðµ¨¿¡¼­, óÀ½À¸·Î Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±º (stem-like CD8 T cell subset)ÀÇ Á¸À縦 ¹àÇûÀ½. Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±ºÀº Ç׿ø ƯÀÌÀûÀÎ T¼¼Æ÷ ¹ÝÀÀÀ» À¯ÁöÇϴµ¥ ÇʼöÀûÀ̸ç, ƯÈ÷³ª ¸é¿ª Ç×¾ÏÄ¡·áÁ¦·Î ³Î¸® »ç¿ëµÇ°í ÀÖ´Â Ç×PD-1/PD-L1 Ç×ü¿¡ ƯÀÌÀûÀ¸·Î ¹ÝÀÀÇÏ¿© T¼¼Æ÷ ¹ÝÀÀÀ» Áõ°­½ÃÅ°´Â ¿ªÇÒÀ» ÇÔ. ÀÌ·¯ÇÑ °á°ú´Â ¸é¿ª Ç׾Ϻо߿¡ »õ·Î¿î Æз¯´ÙÀÓÀ» Á¦°øÇÏ¿´°í, »õ·Î¿î ¸é¿ª Ç×¾ÏÄ¡·áÁ¦ °³¹ß¿¡ Áß¿äÇÑ Å¸°ÙÀ¸·Î »ý°¢µÇ°í ÀÖÀ½.
    º» ¿¬±¸½ÇÀº Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±ºÀÇ »ý¼º ¹× À¯Áö ±âÀÛ¿¡ ´ëÇÏ¿© ´ÙÀ½ÀÇ Ç׸ñµé¿¡ ÃÊÁ¡À» ¸ÂÃß¾î ¿¬±¸ÇÏ°íÀÚ ÇÔ. 1) Àü»çÁ¶Àý ÀÎÀÚ, 2) Ç׿øÁ¦½Ã¼¼Æ÷¿Í T¼¼Æ÷°£ÀÇ »óÈ£ÀÛ¿ë, 3) ¸é¿ªÁ¶Àý ´Ü¹éÁú, 4) Àå³» ¹Ì»ý¹° Á¶¼º

    B. ¸é¿ª Ç×¾ÏÄ¡·áÁ¦ °³¹ß
    1) »õ·Î¿î Ÿ°Ù¿¡ ´ëÇÑ Ç×ü Ä¡·áÁ¦ °³¹ß
    ±â´ÉÀúÇÏµÈ T¼¼Æ÷ÀÇ Àü»çü ºÐ¼® ¹× ÈļºÀ¯ÀüÇÐÀû ºÐ¼®À» ÅëÇÏ¿© »õ·Î¿î ¸é¿ªÁ¶Àý ´Ü¹éÁúµéÀ» ±Ô¸íÇÏ°í, À̵éÀÌ Ç׿ø ƯÀÌÀûÀÎ T¼¼Æ÷¹ÝÀÀ¿¡ ¹ÌÄ¡´Â ¿µÇâÀ» ¹àÈ÷°íÀÚ ÇÔ. ¶ÇÇÑ ¹ÙÀÌ¿ÀÅØ È¸»ç¿ÍÀÇ Çù¾÷¿¬±¸¸¦ ÅëÇÏ¿© »õ·Î¿î ¸é¿ªÁ¶Àý ´Ü¹éÁúµé¿¡ ´ëÇÑ Ç×ü Ä¡·áÁ¦ °³¹ßÀ» ¸ñÇ¥·Î ÇÔ.

    2) ³»Àμº T¼¼Æ÷¸¦ ÀÌ¿ëÇÑ T¼¼Æ÷ Ä¡·áÁ¦ °³¹ß
    CAR (chimeric antigen receptor) T¼¼Æ÷ Ä¡·áÁ¦´Â ´ëÇ¥ÀûÀÎ ¸é¿ª Ç×¾ÏÄ¡·áÁ¦ Áß Çϳª·Î, ¹ÌFDA ½ÂÀÎÀ» ¹Þ¾Æ¼­ Ç÷¾×¾Ï Ä¡·á¿¡ »ç¿ëµÇ°í ÀÖÀ½. ÇÏÁö¸¸ °íÇü¾Ï ¸ðµ¨ÀÇ °æ¿ì, °øÅëÀûÀÎ Á¾¾ç Ç׿øÀÇ ±Ô¸íÀÌ ½±Áö ¾Ê¾Æ¼­ CAR T¼¼Æ÷ Ä¡·áÁ¦ °³¹ßÀÌ ¾î·Á¿ò. À̸¦ ±Øº¹Çϱâ À§ÇÏ¿©, ȯÀÚ ÀÚ½ÅÀÇ Á¾¾ç ƯÀÌÀûÀÎ ³»Àμº T¼¼Æ÷¸¦ ÀÌ¿ëÇÑ »õ·Î¿î T¼¼Æ÷ Ä¡·áÁ¦¸¦ °³¹ßÇÏ°íÀÚ ÇÔ.

    C. ÀÚ°¡¸é¿ªÁúȯ¿¡ ´ëÇÑ Ç×üġ·áÁ¦ °³¹ß
    ÃÖ±Ù ¿¬±¸µé¿¡ µû¸£¸é ¸¶¿ì½º ¸é¿ª ³úô¼ö¿° (EAE, Experimental Autoimmune Encephalomyelitis) ¸ðµ¨ ¹× ¿°Áõ¼º Àå Áúȯ (IBD, Inflammatory Bowel Disease) ¸ðµ¨¿¡¼­µµ Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±ºÀÌ ¹ß°ßµÊ. Èï¹Ì·Ó°Ôµµ ÀÚ°¡¸é¿ªÁúȯ¿¡¼­ ¹ß°ßµÇ´Â Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±ºÀº ¸¸¼º ¹ÙÀÌ·¯½º °¨¿° ¹× Á¾¾ç ¸ðµ¨¿¡¼­ ¹ß°ßµÇ´Â Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±º°ú À¯»çÇÑ Àü»çü ¹ßÇöÆÐÅÏÀ» º¸ÀÓ. º» ¿¬±¸ÆÀÀº ÀÚ°¡¸é¿ªÁúȯ¿¡¼­ Áٱ⼼Æ÷ À¯»ç¼¼Æ÷±ºÀÇ ±â´ÉÀ» Á¶ÀýÇÏ´Â »õ·Î¿î ¸é¿ªÁ¶Àý ´Ü¹éÁúÀ» ±Ô¸íÇÏ°í, À̸¦ ÀÌ¿ëÇÏ¿© T¼¼Æ÷ÀÇ ±â´ÉÀ» ÀúÇØÇÏ´Â »õ·Î¿î Ç×ü Ä¡·áÁ¦¸¦ °³¹ßÇÏ°íÀÚ ÇÔ.

´ëÇ¥¿¬±¸¾÷Àû

  • 1. Im SJ, Konieczny BT, Hudson WH, Masopust D and Ahmed R. PD-1+ stemlike CD8 T cells are resident in lymphoid tissues during persistent LCMV infection. Proc Natl Acad Sci USA (2020) 117(8):4292 PMID: 32034098 (IF: 9.504)

    2. Jansen CS, Prokhnevska N, Master V, Sanda M, Carlisle JW, Bilen MA, Cardenas M, Wilkinson S, Lake R, Sowalsky AG, Valanparambil RM, Hudson WH, McGuire D, Melnick K, Khan AI, Kim K, Chang YM, Kim A, Filson C, Alemozaffar M, Osunkoya AO, Mullane P, Ellis C, Akondy R, Im SJ, Kamphorst A, Reyes A, Liu Y and Kissick HT. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature (2019) 576(7787):465 PMID: 31827286 (IF: 41.577)

    3. Hudson WH, Gensheimer JL, Hashimoto M, Wieland A, Valanparambil RM, Li P, Lin JX, Konieczny BT, Im SJ, Freeman GJ, Leonard WJ, Kissick HT and Ahmed R. Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T cells during chronic infection. Immunity (2019), 51(6):1043 PMID: 31810882 (IF: 19.744)

    4. *Jadhav RR, *Im SJ, *Hu B, Hashimoto M, Li P, Leonard WJ, Greenleaf WJ, ☨Ahmed R and ☨Goronzy JJ. Epigenetic signature of PD-1+TCF1+ CD8 T cells that act as resource cells during chronic viral infection and respond to PD-1 blockade. Proc Natl Acad Sci USA (2019), 116 (28):14113 PMID: 31227606 (IF: 9.504) (*Co-first authors, ☨Co-corresponding authors)

    5. Im SJ, Hashimoto M, Gerner MY, Lee J, Kissick HT, Burger MC, Shan Q, Hale JS, Lee J, Nasti TH, Sharpe AH, Freeman GJ, Germain RN, Nakaya HI, Xue HH and Ahmed R. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature (2016) 537(7620):417. PMID: 27501248 (IF: 40.137)
    - This article is highlighted in News and Views of same issue of Nature (2016) 537(7620):312.